1-Chloromethyl-6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-sulfonic acid amide, a derivative of tetrahydroisoquinoline, induces granulocytic differentiation of the human leukemic HL-60 cells via G0/G1 phase arrest

Sung-Min Ju, Hyun-Ock Pae, Won-Sin Kim, Chai-Ho Lee, Byung-Hun Jeon

Department of Biological Science, College of Natural Sciences, Wonkwang University, Iksan, South Korea.
Department of Bionanochemistry, School of Natural Sciences, Wonkwang University, Iksan, South Korea.
Department of Microbiology and Immunology, Wonkwang University School of Medicine, Iksan, South Korea.
Department of Pathology, College of Korean Medicine, Wonkwang University, Iksan, South Korea;.

DOI: 10.4236/health.2013.55A001                

Abstract

Tetrahydroisoquinolines are known to have various biological effects, including antitumor activity. This study investigated the effect of 1-chloromethyl-6, 7-dimethoxy-3, 4-dihydro-1H-isoquinoline-2-sulfonic acid amide (CDST), a newly synthesized anticancer agent, on cellular differentiation and proliferation in HL-60 cells. Differentiation and proliferation of HL-60 cells were determined through expression of CD11b and CD14 surface antigens using flow cytometry and nitroblue tetrazolium (NBT) assay, and through analysis of cell cycle using propidium iodide staining, western blot analysis and immunoprecipitation, respectively. CDST induced the differentiation of HL-60, as shown by increased expression of differentiation surface antigen CD11b (but no significant change in CD14 expression) and increased NBT-reducing functional activity. DNA flow cytometry analysis indicated that CDST markedly induced a G0/G1 phase arrest of HL-60 cells. Subsequently, we examined the expre-ssion of G0/G1 phase cell cycle-related proteins, including cyclin-dependent kinases (CDKs), cyclins and cyclin dependent kinase inhibitors (CKIs), during the differentiation of HL-60. The levels of CDK2, CDK6, cyclin E and cyclin A were decreased, whereas steady-state levels of CDK4 and cyclin D1 were unaffected. The expression of the p27^Kip1 was markedly increased by CDST, but not p21^WAF1/Cip1. Moreover, CDST markedly enhanced the binding of p27^Kip1 with CDK2 and CDK6, resulting in the reduced activity of both kinases. Taken together, these results demonstrate that CDST is capable of inducing cellular differentiation and growth inhibition through p27^Kip1 protein-related G0/G1 phase arrest in HL-60 cells.

Keywords

Differentiation; G0/G1 Phase Arrest; HL-60 Cells; Tetrahydroisoquinolines; P27Kip1

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Huberman, E. and Callaham, M.F. (1979) Induction of terminal differentiation in human promyelocytic leukemia cells by tumor-promoting agents. Proceedings of the National Academy of Sciences of the United States of America, 76, 1293-1297. doi:10.1073/pnas.76.3.1293
[2]	Rovera, G., Santoli, D. and Damsky, C. (1979) Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proceedings of the National Academy of Sciences of the United States of America, 76, 2779-2783. doi:10.1073/pnas.76.6.2779
[3]	Collins, S.J., Ruscetti, F.W., Gallagher, R.E. and Gallo, R.C. (1978) Terminal differentiation of human promyelocytic leukemia cells induced by dimethyl sulfoxide and other polar compounds. Proceedings of the National Academy of Sciences of the United States of America, 75, 2458-2462.
[4]	Breitman, T.R., Selonick, S.E. and Collins, S.J. (1980) Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proceedings of the National Academy of Sciences of the United States of America, 77, 2946-2940. doi:10.1073/pnas.77.5.2936
[5]	Figarola, J.L., Weng, Y., Lincoln, C., Horne, D. and Rahbar S. (2012) Novel dichlorophenyl urea compounds inhibit proliferation of human leukemia HL-60 cells by inducing cell cycle arrest, differentiation and apoptosis. Investigational New Drugs, 30, 1413-1425. doi:10.1007/s10637-011-9711-8
[6]	Congleton, J., MacDonald, R. and Yen A. (2012) Src inhibitors, PP2 and dasatinib, increase retinoic acid-induced association of Lyn and c-Raf (S259) and enhance MAPK-dependent differentiation of myeloid leukemia cells. Leukemia, 26, 1180-1188. doi:10.1038/leu.2011.390
[7]	Kuo, H.C., Kuo, W.H., Lee, Y.J., Wang, C.J. and Tseng, T.H. (2006) Enhancement of caffeic acid phenethyl ester on all-trans retinoic acid-induced differentiation in human leukemia HL-60 cells. Toxicology and Applied Pharmacology, 216, 80-88. doi:10.1016/j.taap.2006.04.007
[8]	Fabiani, R., Rosignoli, P., De Bartolomeo, A., Fuccelli, R. and Morozzi, G. (2008) Inhibition of cell cycle progression by hydroxytyrosol is associated with upregulation of cyclin-dependent protein kinase inhibitors p21(WAF1/ Cip1) and p27(Kip1) and with induction of differentiation in HL60 cells. Journal of Nutrition, 138, 42-48.
[9]	Powan, P., Saito, N., Suwanborirux, K. and Chanvorachote, P. (2013) Ecteinascidin 770, a tetrahydroisoquinoline alkaloid, sensitizes human lung cancer cells to anoikis. Anticancer Research, 33, 505-512.
[10]	Anan, H., Tanaka, A., Tsuzuki, R., Yokota, M., Yatsu, T. and Fujikura, T. (1996) 4-(3,4-Dihydroxyphenyl)-1,2,3,4-tetrahydroisoquinoline derivatives. II. Their renal vasodilation activity and structure-activity relationship. Chemical and Pharmaceutical Bulletin (Tokyo), 44, 1865-1870.
[11]	Watanuki, S., Matsuura, K., Tomura, Y., Okada, M., Okazaki, T., Ohta, M. and Tsukamoto, S. (2011) Synthesis and pharmacological evaluation of 1-isopropyl-1,2,3,4- tetrahydroisoquinoline derivatives as novel antihypertensive agents. Chemical and Pharmaceutical Bulletin (Tokyo), 59, 1029-1037.
[12]	Okuda, K., Kotake, Y. and Ohta, S. (2006) Parkinsonism-preventing activity of 1-methyl-1,2,3,4-tetrahydroisoquinoline derivatives in C57BL mouse in vivo. Biological and Pharmaceutical Bulletin, 29, 1401-1403. doi:10.1248/bpb.29.1401
[13]	Sakashita, A., Nakamaki, T., Tsuruoka, N., Honma, Y. and Hozumi, M. (1991) Granulocyte colony-stimulating factor, not granulocyte-macrophage colony-stimulating factor, co-operates with retinoic acid on the induction of functional N-formyl-methionyl-phenylalanine receptors in HL-60 cells. Leukemia, 5, 26-31.
[14]	Pae, H.O., Seo, W.G., Kim, N.Y., Oh, G.S., Kim, G.E., Kim, Y.H., Kwak, H.J., Yun, Y.G., Jun, C.D. and Chung, H.T. (2001) Induction of granulocytic differentiation in acute promyelocytic leukemia cells (HL-60) by water-soluble chitosan oligomer. Leukemia Research, 25, 339-346. doi:10.1016/S0145-2126(00)00138-7
[15]	Seo, B.R., Lee, K.W., Ha, J., Park, H.J., Choi, J.W. and Lee, K.T. (2004) Saucernetin-7 isolated from Saururus chinensis inhibits proliferation of human promyelocytic HL-60 leukemia cells via G0/G1 phase arrest and induction of differentiation. Carcinogenesis, 25, 1387-1394. doi:10.1093/carcin/bgh143
[16]	Chen, W.J., Chang, C.Y. and Lin, J.K. (2003) Induction of G1 phase arrest in MCF human breast cancer cells by pentagalloylglucose through the down-regulation of CDK4 and CDK2 activities and up-regulation of the CDK inhibitors p27(Kip) and p21(Cip). Biochemical Pharmacology, 65, 1777-1785. doi:10.1016/S0006-2952(03)00156-4
[17]	Coqueret, O. (2003) New roles for p21 and p27 cell-cycle inhibitors: A function for each cell compartment? Trends in Cell Biology, 13, 65-70. doi:10.1016/S0962-8924(02)00043-0
[18]	Choi, J.H., Shin, K.M., Kim, N.Y., Hong, J.P, Lee, Y.S., Kim, H.J., Park, H.J. and Lee, K.T. (2002) Taraxinic acid, a hydrolysate of sesquiterpene lactone glycoside from the Taraxacum coreanum NAKAI, induces the differentiation of human acute promyelocytic leukemia HL-60 cells. Biological & Pharmaceutical Bulletin, 25, 1446-1450. doi:10.1248/bpb.25.1446
[19]	Chen-Deutsch, X. and Studzinski, G.P. (2012) Dual role of hematopoietic progenitor kinase 1 (HPK1) as a positive regulator of 1α,25-dihydroxyvitamin D-induced differentiation and cell cycle arrest of AML cells and as a mediator of vitamin D resistance. Cell Cycle, 11, 1364-1373. doi:10.4161/cc.19765
[20]	Kokorina, N.A., Granier, C.J., Zakharkin, S.O., Davis, S., Rabson, A.B. and Sabaawy, H.E. (2012) PDCD2 knockdown inhibits erythroid but not megakaryocytic lineage differentiation of human hematopoietic stem/progenitor cells. Experimental Hematology, 40, 1028-1042. doi:10.1016/j.exphem.2012.08.004
[21]	Fang, Y., Zhou, X., Lin, M., Jing, H., Zhong, L., Ying, M., Luo, P., Yang, B. and He, Q. (2010) The ubiquitin-proteasome pathway plays essential roles in ATRA-induced leukemia cells G0/G1 phase arrest and transition into granulocytic differentiation. Cancer Biology & Therapy, 10, 1157-1167.
[22]	Cooper, S. (2001) Revisiting the relationship of the mammalian G1 phase to cell differentiation. Journal of Theoretical Biology, 208, 399-402. doi:10.1006/jtbi.2000.2228
[23]	Jeon, Y., Lee, K.Y., Ko, M.J., Lee, Y.S., Kang, S. and Hwang, D.S. (2007) Human TopBP1 participates in cyclin E/CDK2 activation and preinitiation complex assembly during G1/ S transition. The Journal of Biological Chemistry, 282, 14882-14890.
[24]	Matsumoto, A. and Nakayama, K.I. (2013) Role of key regulators of the cell cycle in maintenance of hematopoietic stem cells. Biochimica et Biophysica Acta, 1830, 23352340.
[25]	Dimberg, A. and Oberg, F. (2003) Retinoic acid-induced cell cycle arrest of human myeloid cell lines. Leukemia and Lymphoma, 44, 1641-1650.